TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29493	88702;88703;88704	chr2:178554982;178554981;178554980	chr2:179419709;179419708;179419707
N2AB	27852	83779;83780;83781	chr2:178554982;178554981;178554980	chr2:179419709;179419708;179419707
N2A	26925	80998;80999;81000	chr2:178554982;178554981;178554980	chr2:179419709;179419708;179419707
N2B	20428	61507;61508;61509	chr2:178554982;178554981;178554980	chr2:179419709;179419708;179419707
Novex-1	20553	61882;61883;61884	chr2:178554982;178554981;178554980	chr2:179419709;179419708;179419707
Novex-2	20620	62083;62084;62085	chr2:178554982;178554981;178554980	chr2:179419709;179419708;179419707
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-146
• Domain position: 50
• Structural Position: 131
• Q(SASA): 0.7279
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/M	rs955762474	0.091	1.0	N	0.455	0.287	0.299086750705	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	1.66003E-04
T/M	rs955762474	0.091	1.0	N	0.455	0.287	0.299086750705	gnomAD-4.0.0	2.12127E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	3.46861E-04	2.15876E-05	1.15939E-05	6.62712E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.0642	likely_benign	0.0633	benign	-0.226	Destabilizing	0.994	D	0.337	neutral	N	0.377054257	None	None	N
T/C	0.4071	ambiguous	0.3931	ambiguous	-0.165	Destabilizing	1.0	D	0.477	neutral	None	None	None	None	N
T/D	0.274	likely_benign	0.2427	benign	0.106	Stabilizing	1.0	D	0.466	neutral	None	None	None	None	N
T/E	0.2286	likely_benign	0.2114	benign	0.018	Stabilizing	1.0	D	0.465	neutral	None	None	None	None	N
T/F	0.2866	likely_benign	0.2557	benign	-0.804	Destabilizing	0.269	N	0.289	neutral	None	None	None	None	N
T/G	0.1822	likely_benign	0.1779	benign	-0.327	Destabilizing	1.0	D	0.449	neutral	None	None	None	None	N
T/H	0.2571	likely_benign	0.2458	benign	-0.614	Destabilizing	1.0	D	0.529	neutral	None	None	None	None	N
T/I	0.1671	likely_benign	0.1478	benign	-0.083	Destabilizing	0.998	D	0.429	neutral	None	None	None	None	N
T/K	0.1669	likely_benign	0.1596	benign	-0.261	Destabilizing	1.0	D	0.463	neutral	N	0.364586392	None	None	N
T/L	0.1074	likely_benign	0.1022	benign	-0.083	Destabilizing	0.983	D	0.413	neutral	None	None	None	None	N
T/M	0.0942	likely_benign	0.0922	benign	0.053	Stabilizing	1.0	D	0.455	neutral	N	0.452706809	None	None	N
T/N	0.1174	likely_benign	0.1139	benign	-0.003	Destabilizing	1.0	D	0.419	neutral	None	None	None	None	N
T/P	0.0801	likely_benign	0.0833	benign	-0.103	Destabilizing	0.999	D	0.439	neutral	N	0.376880899	None	None	N
T/Q	0.1996	likely_benign	0.2011	benign	-0.242	Destabilizing	1.0	D	0.455	neutral	None	None	None	None	N
T/R	0.139	likely_benign	0.1353	benign	0.01	Stabilizing	1.0	D	0.441	neutral	N	0.403624783	None	None	N
T/S	0.0956	likely_benign	0.0966	benign	-0.182	Destabilizing	0.998	D	0.363	neutral	N	0.379342414	None	None	N
T/V	0.1231	likely_benign	0.1139	benign	-0.103	Destabilizing	0.992	D	0.347	neutral	None	None	None	None	N
T/W	0.5688	likely_pathogenic	0.5497	ambiguous	-0.851	Destabilizing	1.0	D	0.551	neutral	None	None	None	None	N
T/Y	0.2979	likely_benign	0.2793	benign	-0.543	Destabilizing	0.995	D	0.527	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.